Impact of the Gram-Negative-Selective Inhibitor MAC13243 on In Vitro Simulated Gut Microbiota
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Impact of the Gram-Negative-Selective Inhibitor MAC13243 on In Vitro Simulated Gut Microbiota. / Frisinger, Frida Svanberg; Pirolo, Mattia; Ng, Duncan Y.K.; Mao, Xiaotian; Nielsen, Dennis Sandris; Guardabassi, Luca.
In: Pharmaceuticals, Vol. 15, No. 6, 731, 2022.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Impact of the Gram-Negative-Selective Inhibitor MAC13243 on In Vitro Simulated Gut Microbiota
AU - Frisinger, Frida Svanberg
AU - Pirolo, Mattia
AU - Ng, Duncan Y.K.
AU - Mao, Xiaotian
AU - Nielsen, Dennis Sandris
AU - Guardabassi, Luca
N1 - Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022
Y1 - 2022
N2 - New Gram-negative-selective antimicrobials are desirable to avoid perturbations in the gut microbiota leading to antibiotic-induced dysbiosis. We investigated the impact of a prototype drug (MAC13243) interfering with the Gram-negative outer membrane protein LolA on the faecal microbiota. Faecal suspensions from two healthy human donors were exposed to MAC13243 (16, 32, or 64 mg/L) using an in vitro gut model (CoMiniGut). Samples collected 0, 4, and 8 h after exposure were subjected to viable cell counts, 16S rRNA gene quantification and V3-V4 sequencing using the Illumina MiSeq platform. MAC13243 exhibited concentration-dependent killing of coliforms in both donors after 8 h. Concentrations of ≤32 mg/L reduced the growth of aerobic bacteria without influencing the microbiota composition and diversity. An expansion of Firmicutes at the expense of Bacteroidetes and Actinobacteria was observed in the faecal microbiota from one donor following exposure to 64 mg/L of MAC13242. At all concentrations tested, MAC13243 did not lead to the proliferation of Escherichia coli nor a reduced abundance of beneficial bacteria, which are typical changes observed in antibiotic-induced dysbiosis. These results support our hypothesis that a drug interfering with a specific target in Gram-negative bacteria has a low impact on the commensal gut microbiota and, therefore, a low risk of inducing dysbiosis.
AB - New Gram-negative-selective antimicrobials are desirable to avoid perturbations in the gut microbiota leading to antibiotic-induced dysbiosis. We investigated the impact of a prototype drug (MAC13243) interfering with the Gram-negative outer membrane protein LolA on the faecal microbiota. Faecal suspensions from two healthy human donors were exposed to MAC13243 (16, 32, or 64 mg/L) using an in vitro gut model (CoMiniGut). Samples collected 0, 4, and 8 h after exposure were subjected to viable cell counts, 16S rRNA gene quantification and V3-V4 sequencing using the Illumina MiSeq platform. MAC13243 exhibited concentration-dependent killing of coliforms in both donors after 8 h. Concentrations of ≤32 mg/L reduced the growth of aerobic bacteria without influencing the microbiota composition and diversity. An expansion of Firmicutes at the expense of Bacteroidetes and Actinobacteria was observed in the faecal microbiota from one donor following exposure to 64 mg/L of MAC13242. At all concentrations tested, MAC13243 did not lead to the proliferation of Escherichia coli nor a reduced abundance of beneficial bacteria, which are typical changes observed in antibiotic-induced dysbiosis. These results support our hypothesis that a drug interfering with a specific target in Gram-negative bacteria has a low impact on the commensal gut microbiota and, therefore, a low risk of inducing dysbiosis.
KW - antibiotic targets
KW - Escherichia coli
KW - LolA
KW - microbiome
KW - selective antimicrobial activity
U2 - 10.3390/ph15060731
DO - 10.3390/ph15060731
M3 - Journal article
C2 - 35745650
AN - SCOPUS:85132715287
VL - 15
JO - Pharmaceuticals
JF - Pharmaceuticals
SN - 1424-8247
IS - 6
M1 - 731
ER -
ID: 313495588